Severe Hypercalcemia Due to Hyperparathyroidism and CYP24A1

Jannel Liu, Peter Angelos, Maan Barhoum, Rajesh Jain
JCEM Case Reports, Volume 1, Issue 4, July 2023, luad071
https://doi.org/10.1210/jcemcr/luad071

Abstract

Pathogenic variants of CYP24A1 are associated with hypercalcemia due to disruptions in the ability of 24-hydroxylase to break down 1,25-dihydroxyvitamin D (1,25-DHVD). A case involving a heterozygous pathogenic variant of CYP24A1 and primary hyperparathyroidism leading to severe hypercalcemia has not been previously reported. A 23-year-old woman presented with fatigue and was found to be hypercalcemic at 13.8 mg/dL [reference range, 8.4–10.2 pg/mL]. Her parathyroid hormone (PTH) was 62 pg/mL [reference range, 19–88 pg/mL] and 1,25-DHVD was elevated to 242.7 pg/mL [reference range, 18–72 pg/mL]. Other laboratory workup was unrevealing. She had a bone scan, whole body CT scan, and thyroid ultrasound that were normal. Her 25-hydroxy-vitamin D to 24,25-dihydroxy-vitamin D ratio was elevated at 25.18 (normal, < 25). Because of concern for primary hyperparathyroidism, she was referred to an endocrine surgeon and underwent a parathyroidectomy with the removal of a 3.5-gram adenoma. Pathology showed a parafibromin-deficient parathyroid neoplasm. Genetic testing demonstrated a heterozygous pathogenic variant in CYP24A1. Three weeks after surgery, PTH was 14 pg/mL (1.48 pmol/L), calcium and 1,25-DHVD normalized. In summary, we report a case where a patient with severe symptomatic hypercalcemia was found to have primary hyperparathyroidism exacerbated by an underlying heterozygous pathogenic variant in CYP24A1.

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